Photosymbiosis reduces the environmental stress response under a heat challenge in a facultatively symbiotic coral.

The symbiosis between corals and dinoflagellates of the family Symbiodiniaceae is sensitive to environmental stress. The oxidative bleaching hypothesis posits that extreme temperatures lead to accumulation of photobiont-derived reactive oxygen species ROS, which exacerbates the coral environmental stress response (ESR). To understand how photosymbiosis modulates coral ESRs, these responses must be explored in hosts in and out of symbiosis. We leveraged the facultatively symbiotic coral Astrangia poculata, which offers an opportunity to uncouple the ESR across its two symbiotic phenotypes (brown, white). Colonies of both symbiotic phenotypes were exposed to three temperature treatments for 15 days: (i) control (static 18 °C), (ii) heat challenge (increasing from 18 to 30 °C), and (iii) cold challenge (decreasing from 18 to 4 °C) after which host gene expression was profiled. Cold challenged corals elicited widespread differential expression, however, there were no differences between symbiotic phenotypes. In contrast, brown colonies exhibited greater gene expression plasticity under heat challenge, including enrichment of cell cycle pathways involved in controlling photobiont growth. While this plasticity was greater, the genes driving this plasticity were not associated with an amplified environmental stress response (ESR) and instead showed patterns of a dampened ESR under heat challenge. This provides nuance to the oxidative bleaching hypothesis and suggests that, at least during the early onset of bleaching, photobionts reduce the host's ESR under elevated temperatures in A. poculata.

Reef environments shape microbial partners in a highly connected coral population.

Evidence is mounting that composition of microorganisms within a host can play an essential role in total holobiont health. In corals, for instance, studies have identified algal and bacterial taxa that can significantly influence coral host function and these communities depend on environmental context. However, few studies have linked host genetics to algal and microbial partners across environments within a single coral population. Here, using 2b-RAD sequencing of corals and metabarcoding of their associated algal (ITS2) and bacterial (16S) communities, we show evidence that reef zones (locales that differ in proximity to shore and other environmental characteristics) structure algal and bacterial communities at different scales in a highly connected coral population (Acropora hyacinthus) in French Polynesia. Fore reef (FR) algal communities in Mo'orea were more diverse than back reef (BR) communities, suggesting that these BR conditions constrain diversity. Interestingly, in FR corals, host genetic diversity correlated with bacterial diversity, which could imply genotype by genotype interactions between these holobiont members. Our results illuminate that local reef conditions play an important role in shaping unique host-microbial partner combinations, which may have fitness consequences for dispersive coral populations arriving in novel environments.

Symbiosis maintenance in the facultative coral, Oculina arbuscula, relies on nitrogen cycling, cell cycle modulation, and immunity.

Symbiosis with unicellular algae in the family Symbiodiniaceae is common across tropical marine invertebrates. Reef-building corals offer a clear example of cellular dysfunction leading to a dysbiosis that disrupts entire ecosystems in a process termed coral bleaching. Due to their obligate symbiotic relationship, understanding the molecular underpinnings that sustain this symbiosis in tropical reef-building corals is challenging, as any aposymbiotic state is inherently coupled with severe physiological stress. Here, we leverage the subtropical, facultatively symbiotic and calcifying coral Oculina arbuscula to investigate gene expression differences between aposymbiotic and symbiotic branches within the same colonies under baseline conditions. We further compare gene ontology (GO) and KOG enrichment in gene expression patterns from O. arbuscula with prior work in the sea anemone Exaiptasia pallida (Aiptasia) and the salamander Ambystoma maculatum-both of which exhibit endophotosymbiosis with unicellular algae. We identify nitrogen cycling, cell cycle control, and immune responses as key pathways involved in the maintenance of symbiosis under baseline conditions. Understanding the mechanisms that sustain a healthy symbiosis between corals and Symbiodiniaceae algae is of urgent importance given the vulnerability of these partnerships to changing environmental conditions and their role in the continued functioning of critical and highly diverse marine ecosystems.

Correction to: Coral Symbiodinium Community Composition Across the Belize Mesoamerican Barrier Reef System is Influenced by Host Species and Thermal Variability.

The authors regret that acknowledgment for Dr. Adrian Marchetti was omitted from the manuscript. The correct acknowledgment is written below.

Coral Symbiodinium Community Composition Across the Belize Mesoamerican Barrier Reef System is Influenced by Host Species and Thermal Variability.

Reef-building corals maintain a symbiotic relationship with dinoflagellate algae of the genus Symbiodinium, and this symbiosis is vital for the survival of the coral holobiont. Symbiodinium community composition within the coral host has been shown to influence a coral's ability to resist and recover from stress. A multitude of stressors including ocean warming, ocean acidification, and eutrophication have been linked to global scale decline in coral health and cover in recent decades. Three distinct thermal regimes (highTP, modTP, and lowTP) following an inshore-offshore gradient of declining average temperatures and thermal variation were identified on the Belize Mesoamerican Barrier Reef System (MBRS). Quantitative metabarcoding of the ITS-2 locus was employed to investigate differences and similarities in Symbiodinium genetic diversity of the Caribbean corals Siderastrea siderea, S. radians, and Pseudodiploria strigosa between the three thermal regimes. A total of ten Symbiodinium lineages were identified across the three coral host species. S. siderea was associated with distinct Symbiodinium communities; however, Symbiodinium communities of its congener, S. radians and P. strigosa, were more similar to one another. Thermal regime played a role in defining Symbiodinium communities in S. siderea but not S. radians or P. strigosa. Against expectations, Symbiodinium trenchii, a symbiont known to confer thermal tolerance, was dominant only in S. siderea at one sampled offshore site and was rare inshore, suggesting that coral thermal tolerance in more thermally variable inshore habitats is achieved through alternative mechanisms. Overall, thermal parameters alone were likely not the only primary drivers of Symbiodinium community composition, suggesting that environmental variables unrelated to temperature (i.e., light availability or nutrients) may play key roles in structuring coral-algal communities in Belize and that the relative importance of these environmental variables may vary by coral host species.

Exploring the role of Micronesian islands in the maintenance of coral genetic diversity in the Pacific Ocean.

Understanding how genetic diversity is maintained across patchy marine environments remains a fundamental problem in marine biology. The Coral Triangle, located in the Indo-West Pacific, is the centre of marine biodiversity and has been proposed as an important source of genetic diversity for remote Pacific reefs. Several studies highlight Micronesia, a scattering of hundreds of small islands situated within the North Equatorial Counter Current, as a potentially important migration corridor. To test this hypothesis, we characterized the population genetic structure of two ecologically important congeneric species of reef-building corals across greater Micronesia, from Palau to the Marshall Islands. Genetic divergences between islands followed an isolation-by-distance pattern, with Acropora hyacinthus exhibiting greater genetic divergences than A. digitifera, suggesting different migration capabilities or different effective population sizes for these closely related species. We inferred dispersal distance using a biophysical larval transport model, which explained an additional 15-21% of the observed genetic variation compared to between-island geographical distance alone. For both species, genetic divergence accumulates and genetic diversity diminishes with distance from the Coral Triangle, supporting the hypothesis that Micronesian islands act as important stepping stones connecting the central Pacific with the species-rich Coral Triangle. However, for A. hyacinthus, the species with lower genetic connectivity, immigration from the subequatorial Pacific begins to play a larger role in shaping diversity than input from the Coral Triangle. This work highlights the enormous dispersal potential of broadcast-spawning corals and identifies the biological and physical drivers that influence coral genetic diversity on a regional scale.

Evidence for a host role in thermotolerance divergence between populations of the mustard hill coral (Porites astreoides) from different reef environments.

Studying the mechanisms that enable coral populations to inhabit spatially varying thermal environments can help evaluate how they will respond in time to the effects of global climate change and elucidate the evolutionary forces that enable or constrain adaptation. Inshore reefs in the Florida Keys experience higher temperatures than offshore reefs for prolonged periods during the summer. We conducted a common garden experiment with heat stress as our selective agent to test for local thermal adaptation in corals from inshore and offshore reefs. We show that inshore corals are more tolerant of a 6-week temperature stress than offshore corals. Compared with inshore corals, offshore corals in the 31 °C treatment showed significantly elevated bleaching levels concomitant with a tendency towards reduced growth. In addition, dinoflagellate symbionts (Symbiodinium sp.) of offshore corals exhibited reduced photosynthetic efficiency. We did not detect differences in the frequencies of major (>5%) haplotypes comprising Symbiodinium communities hosted by inshore and offshore corals, nor did we observe frequency shifts ('shuffling') in response to thermal stress. Instead, coral host populations showed significant genetic divergence between inshore and offshore reefs, suggesting that in Porites astreoides, the coral host might play a prominent role in holobiont thermotolerance. Our results demonstrate that coral populations inhabiting reefs <10-km apart can exhibit substantial differences in their physiological response to thermal stress, which could impact their population dynamics under climate change.

Inverting amplifier genetic circuit performance.

A synthetic genetic circuit has been designed whose topology and function echo those of an electronic inverting amplifier. Several variants of this circuit have been built in our laboratory. This paper reports on the testing of one of these variants and contributes to the field both in terms of evaluating the specific amplifier performance and in terms of providing a methodology for performance evaluation of analog genetic circuits. An input source was created and partially calibrated. It was then used to test the circuit through both fluorometer measurements and flow cytometry. In the discussion, consideration is given to cellular loading by the synthetic circuits and the resulting impact on circuit performance. Models developed earlier are compared with the experimental results. The circuit does indeed perform as an inverting amplifier.

The SV stent study: a prospective, multicentre, angiographic evaluation of the BiodivYsio phosphorylcholine coated small vessel stent in small coronary vessels.

OBJECTIVE: To evaluate the use of the phosphorylcholine (PC) coated BiodivYsio small vessel (SV) stent in native coronary vessels of small calibre. DESIGN AND SETTING: Prospective, multi-centre, multi-national registry with 6-month clinical and core-lab angiographic follow-up. Adverse events were adjudicated by a Clinical Events Committee (CEC) and included peri-procedural analysis of cardiac enzymes. PATIENTS: Patients with signs or symptoms of ischaemia with an identified target lesion in an epicardial vessel with reference diameter 2.0-2.75 mm were enrolled. Intervention in other epicardial territories in the same patient was permitted. RESULTS: Recruitment of 150 consecutive lesions (in 143 patients) was completed in 19 centres in Europe and Israel. The stent was deployed successfully in all but one lesion. At 6 months, 1 patient (1%) had experienced sudden cardiac death, 4 further patients (3%) had a non-Q wave MI, and a further 24 patients (17%) had repeat revascularisation of a study target vessel. The mean reference vessel diameter prior to stenting was 2.2 mm (S.D. 0.4). Mean minimal luminal diameters at pre-procedure, post procedure and follow-up were 0.6 mm (S.D. 0.3), 2.0 mm (S.D. 0.4) and 1.2 mm (S.D. 0.6), respectively. The late lumen loss index was 0.55 (S.D. 0.53) with a binary restenosis rate of 32%. CONCLUSIONS: In stenting of selected lesions in small vessels, the BiodivYsio SV stent demonstrated high rates of implant success. The rates of major adverse cardiac events (MACE), angiographic restenosis and repeat revascularisation are similar to those reported in other small vessel bare metal stent studies.

Consequences of deterministic and stochastic modeling of a promoter.

For an engineered genetic oscillator, deterministic analysis indicates sustained oscillations and stochastic simulations show irregular or absent oscillations. Since the major difference is in the modeling of the promoters, we have performed a detailed analysis of a generic repressible promoter system. Deterministic, stochastic, thermodynamic, and hybrid models were developed for the promoter. The average behavior of the stochastic model converged to the thermodynamic model. The deterministic model is a special case of the thermodynamic model. The hybrid model could lock into the off state. Adding an unrelated background reaction allowed it to exit that state. Increasing the background rate allowed the hybrid model to converge to thermodynamic and stochastic model. Adding a background reaction to the stochastic oscillator simulation noticeably improved its performance.

Systemic platelet effects of contrast media: implications for cardiologic research and clinical practice.

BACKGROUND: Angiographic contrast media cause platelet activation and decrease aggregability in vitro. We have previously shown in vitro a significant antiplatelet effect of contrast media at the concentrations obtained locally in the coronary artery during angioplasty. It is not known, however, whether a systemic effect is present. METHOD: Thirty patients undergoing diagnostic coronary angiography were prospectively randomized to receive the nonionic medium iohexol, ionic low-molecular-weight medium ioxaglate, or ionic high-molecular-weight medium diatrizoate. Platelet aggregability was measured before and after the investigation with whole blood electrical impedance aggregometry (WBEA) with collagen agonist and the PFA-100 (Dade, Miami, Fla) platelet function analyzer with combined shear, collagen, and adenosine diphosphate as agonists. RESULTS: With WBEA, with iohexol no difference in impedance change was seen: (medians and ranges) before, 9.8 Omega (4.8-19.2 Omega) versus after, 9.6 Omega (2-19.2 Omega) (P not significant [NS]). With ioxaglate a significant fall was seen: before, 8.6 Omega (6.4-15.2 Omega) versus after, 6.6 Omega (0-12.4 Omega) (P =.004). With diatrizoate a significant and greater fall was seen: before, 10.8 Omega (6.4-17.6 Omega) versus after, 6.6 Omega (0-10.8 Omega) (P =.002). With PFA, no difference in closure time was seen with any medium: iohexol before, 99 seconds (79-142 seconds) versus after, 142 seconds (63-128 seconds) (P NS); ioxaglate before, 120 seconds (75-258 seconds) versus after, 95 seconds (74-258 seconds) (P NS); and diatrizoate before, 114.5 seconds (65-250 seconds) versus after, 100.5 seconds (72-300 seconds) (P NS). CONCLUSIONS: Ionic but not nonionic contrast media have a systemic antiplatelet effect at diagnostic angiographic doses when measured with WBEA. Such an effect has not been shown before. This may explain the observed improved clinical outcome with ionic contrast media but also might confound platelet studies in coronary angioplasty.

Evaluation of free-breathing three-dimensional magnetic resonance coronary angiography with hybrid ordered phase encoding (HOPE) for the detection of proximal coronary artery stenosis.

We evaluated free-breathing, prospective navigator-gated, three-dimensional (3D) magnetic resonance coronary angiography (MRCA) with hybrid ordered phase-encoding (HOPE), in the detection of proximal coronary artery stenosis. The coronary arteries were imaged in 46 patients undergoing cardiac catheterization. The mean scan time was 48 minutes. The mean arterial length (mm) visualized was left main stem (LMS) 11.7 (SD 4.5), left anterior descending (LAD) 30.1 (SD 11.1), circumflex (LCx) 15.5 (SD 8.6), and right (RCA) 56.2 (SD 20.8). Twenty-three patients had coronary artery disease with 47 significant stenoses on cardiac catheterization. All LMS were normal on both catheterization and MRCA. MRCA sensitivity was highest for the LAD (89% CI 65%-99%) and RCA (76% CI 50%-93%), but lower for the LCx (50% CI 21%-79%). Specificity ranged from 72%-100%. Improvements in image quality, length of vessel seen, and specific imaging of the LCx are required for MRCA to become an alternative to cardiac catheterization.

Coronary artery disease as the cause of incident heart failure in the population.

AIMS: New approaches in the treatment of ischaemic left ventricular dysfunction, including revascularization, make it increasingly important to identify heart failure cases resulting from coronary artery disease. Without angiography these cases may be missed. We investigated the frequency of coronary artery disease in incident cases of heart failure in the population. METHODS AND RESULTS: We identified all incident cases of heart failure in a population of 292 000 in South London, U.K. by monitoring patients admitted to hospital and through a rapid access heart failure clinic. The presence and severity of coronary artery disease was identified by coronary angiography in patients under 75 years. Myocardial perfusion scanning was used to elucidate the aetiological significance of the coronary artery disease and identify hibernating myocardium. Three hundred and thirty-two cases of new heart failure were identified over 15 months. One hundred and thirty-six cases were under 75 years and angiography was undertaken in 99/136 (73%). Coronary artery disease was the aetiology in 71/136 (52%). In 18 of these 71 cases (25%), the aetiology was not recognised to be due to coronary artery disease prior to angiography, including eight cases with hibernating myocardium. CONCLUSION: Coronary artery disease is the cause of 52% (95% CI 43-61%) of incident heart failure in the general population under 75 years. Clinical assessment without angiography under-estimates the proportion of patients with coronary artery disease, and fails to identify those patients who may benefit from revascularization.

Clinical presentation and diagnosis of coronary artery disease: stable angina.

Angina pectoris is a clinical syndrome of discomfort in the chest, jaw, arm, or other sites which is associated with myocardial ischaemia. The nature of angina has many individual variations, and it is easier first to consider the typical syndrome. It is hard to better the descriptions of William Heberden: There is a disorder of the breast, marked with strong and peculiar symptoms, considerable for the danger belonging to it.... Those who are afflicted with it are seized, while they are walking, and more particularly when they walk soon after eating, with a painful and most disagreeable sensation in the breast.... the moment they stand still all this uneasiness vanishes. After it has continued some months, it will not cease so instantaneous upon standing still ... (most) whom I have seen, who are at least twenty, were men, and almost all above 50 years old, and most of them with a short neck, and inclining to be fat.... But the natural tendency of this illness be to kill the patients suddenly.... The os sterni is usually pointed to as the seat of this malady ... and sometimes there is with it a pain about the middle of the left arm. The usual cause of myocardial ischaemia is coronary atherosclerosis. Other diseases of the coronary arteries (emboli, spasm, vasculitis, Kawasaki disease, congenital anomalies), other cardiac diseases (hypertrophic cardiomyopathy, severe hypertension, severe aortic valve disease), and high output states (severe anaemia, thyrotoxicosis) are all uncommon or rare causes of angina. However, while angina is usually associated with atherosclerotic coronary artery disease, the converse is not always true. The condition of coronary atherosclerosis is very common (fatty streaks and more advanced plaques are almost universal in adults in industrialised countries) but it does not always cause myocardial ischaemia. Furthermore, myocardial ischaemia may present other than with angina - for each presentation there is a wide differential diagnosis.

Invasive investigations and revascularisation.

Invasive investigation of coronary artery disease is relatively expensive, and carries risks including a mortality of approximately 1 in 2000. It would not be practical or appropriate to perform invasive investigation in all patients with a clinical diagnosis of coronary artery disease, still less in the large numbers with chest pain and possible angina. Clinicians will refer for invasive investigation those: (i) with a high level of angina, needing revascularisation on symptomatic grounds; and (ii) who are likely to have a poor prognosis with medical treatment, and thus likely to benefit from revascularisation. Not all of these patients will have a high level of symptoms.

Diurnal variation in platelet aggregation iwth the PFA-100 platelet function analyser.

BACKGROUND: Myocardial infarction is commoner in the morning, and previous small studies suggesting diurnal variation in platelet aggregation have been limited to optical aggregometry with platelet-rich plasma and low shear. This phenomenon was studied using whole blood at high shear rates. METHOD: Fifteen healthy volunteers were venesected at 0800 hrs supine in bed immediately before rising, at 0830 hrs 30 min after rising, at 1200 hrs and 1700 hrs. Samples underwent the high shear method of PFA-100 using additional chemical agonists of collagen with ADP or collagen with epinephrine. PFA-100 results are reported as closure time of the experimental aperture in seconds, a longer time indicating less platelet aggregation. RESULTS: With both epinephrine and ADP, a non-significant shortening of closure time was seen on rising. Subsequently, with both agonists the closure time lengthened through the day. With ADP the difference was small (medians 0830 hrs: 85 s, 1700 hrs: 87.5 s) but statistically significant (p = 0.03). With epinephrine it was much more marked (medians 0830 hrs: 114.3 s, 1700 hrs: 140.5 s) and highly significant (p = 0.002). CONCLUSIONS: These findings demonstrate a diurnal rhythm in platelet function using whole blood at high shear rates. This is likely to be more applicable to the in vivo situation than previously reported optical aggregometry studies.

Neuronal intranuclear inclusion disease and juvenile parkinsonism.

Juvenile parkinsonism (onset age <20 yrs) is uncommon and few cases with neuropathologic confirmation have been reported. We present the case of a 17-year-old boy who presented with asymmetric arm tremor and bulbar symptoms. His paternal great aunt had parkinsonism with onset at age 22 years. Examination revealed parkinsonism in the absence of additional neurologic signs except for delayed pupillary responses to light. He responded well to levodopa but developed motor fluctuations and disabling dyskinesias after 3 years of treatment. Following attempted withdrawal of levodopa at age 24 years, he developed severe aspiration pneumonia complicated by cardiorepiratory arrests and he died 6 months later. At autopsy, the dominant histologic feature was wide-spread neuronal hyaline intranuclear inclusions. Neuronal depletion was observed in the substantia nigra, locus ceruleus, and, to a lesser extent, in the frontal cortex, and inclusions were particularly prominent in these areas. Inclusions were immunoreactive for ubiquitin and were typical of those seen in neuronal intranuclear inclusion disease (NIID), a rare, multisytem neurodegenerative disease. NIID should be considered in the differential diagnosis of juvenile parkinsonism. A link between NIID and hereditary neurodegenerative disorders characterized by expanded polyglutamine tracts is supported by the similar appearance of intranuclear inclusions in both conditions and by a family history in some cases of NIID.

Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease.

Huntington's disease (HD) is a fatal inherited neurodegenerative disorder characterized by personality changes, motor impairment, and subcortical dementia. HD is one of a number of diseases caused by expression of an expanded polyglutamine repeat. We have developed several lines of mice that are transgenic for exon 1 of the HD gene containing an expanded CAG sequence. These mice exhibit a defined neurological phenotype along with neuronal changes that are pathognomonic for the disease. We have previously observed the appearance of neuronal intranuclear inclusions, but did not find evidence for neurodegeneration. In this study, we report that all lines of these mice develop a late onset neurodegeneration within the anterior cingulate cortex, dorsal striatum, and of the Purkinje neurons of the cerebellum. Dying neurons characteristically exhibit neuronal intranuclear inclusions, condensation of both the cytoplasm and nucleus, and ruffling of the plasma membrane while maintaining ultrastructural preservation of cellular organelles. These cells do not develop blebbing of the nucleus or cytoplasm, apoptotic bodies, or fragmentation of DNA. Neuronal death occurs over a period of weeks not hours. We also find degenerating cells of similar appearance within these same regions in brains of patients who had died with HD. We therefore suggest that the mechanism of neuronal cell death in both HD and a transgenic mouse model of HD is neither by apoptosis nor by necrosis.